“Drug Watch” Sent Back To The Drawing Board; FDA Turning To MedWatch?

FDA is considering proactive communication of early adverse event reports from its MedWatch monitoring system as the agency reassesses its proposed Drug Watch website for emerging safety information.

Drug Watch "is an open discussion at the agency right now and one that we take very seriously....We are looking at how to revise that policy and that guidance," Deputy Commissioner for Medical & Scientific Affairs Scott Gottlieb said during a Food & Drug Law Institute conference in Washington, D.C., Dec. 5.

"One of the ideas we've talked about is the creation of a regular report, something akin to CDC's morbidity and mortality report, where we report off the data from the MedWatch database."

The Centers for Disease Control & Prevention's Morbidity & Mortality Weekly Report is a data reporting mechanism that relays information about disease outbreaks to the public, accompanied by case studies and short reports.

By relying on dissemination of raw data from adverse event reports, FDA is seeking to avoid some of the criticisms associated with its original Drug Watch proposal. The website would describe emerging safety concerns about marketed drugs, with a disclaimer that the data is still under review (¹ (Also see "FDA Rx Safety Website Will Include Drugs With Emerging Off-Label Issues" - Pink Sheet, 9 May, 2005.), p. 3).

Sponsors have been concerned about the release of unsubstantiated drug safety information before FDA has fully evaluated its significance or decided upon regulatory action.

"I don't have the same concerns about the MedWatch database being released and used in ways by physicians and patients that could confuse their decision-making or impact their decision-making in a negative way," Gottlieb explained.

"When you are talking about the MedWatch data, it's such raw information that most reasonable people, especially clinicians, wouldn't act on it in terms of how they practice medicine, but it would prompt more vigilance," Gottlieb explained.

With regular reporting from the MedWatch database, FDA anticipates more physicians would submit adverse event reports, Gottlieb explained.

In an effort to learn how to best release emerging risk management information, FDA plans to initiate a survey among clinicians to evaluate how they are currently using this kind of information in their clinical practice, Gottlieb said.

FDA expects to implement the survey in approximately eight months, but will start the process with focus groups in one to two months.

Finding Middle Ground

Other FDA officials have indicated that the agency is rethinking its original proposal for the Drug Watch initiative. At the FDA/CMS Summit for Biopharmaceutical Executives, sponsored by Windhover Information's The RPM Report, on Nov. 30, Center for Drug Evaluation & Research Director Steven Galson announced "we are going to have to go back to the drawing board."

"This is one of the most challenging, if not the most challenging policy issues, that's in front of me and in front of the agency," Galson said.

Most of the comments the agency has received regarding Drug Watch have been negative (² (Also see "FDA "Drug Watch" Listing Removal Criteria Need Greater Clarity - PhRMA" - Pink Sheet, 15 Aug, 2005.), p. 7). "There was pretty general disagreement with the idea of the Drug Watch as we had originally conceived it," Galson acknowledged.

The CDER chief emphasized the difficulty of determining the appropriate time to release drug safety information to the public.

The agency comes under fire for holding onto information for too long and not publicizing potential safety risks, he noted, but others - particularly industry - contend that releasing early, unsubstantiated drug safety information can be confusing for both physicians and patients.

"The right answer is somewhere in the middle. But the question is, where in the middle is the answer?"

In addition to refining its communication of early risk information, FDA should also work to improve its methods for collecting and advertising early safety data, Pfizer Senior VP-Science & Technology Peter Corr noted at the Windhover event.

FDA Should Start With Better Data

Simply identifying signals early in the process is not the answer to communication of safety data, Corr said. "Current signals are really hypotheses, they are not fact."

"Spontaneous reporting systems that lead to a collection of information [are] often very vague, and not prospectively defined and difficult to interpret."

FDA has taken steps to move beyond data collection through its spontaneous Adverse Events Reporting System. The agency recently entered into contracts with four organizations - Kaiser Foundation, Vanderbilt University, Harvard Pilgrim Health and Igenex - to use their databases to effectively identify early drug safety signals (³ (Also see "FDA Postmarketing Surveillance System Adds Kaiser Retrospective Database" - Pink Sheet, 3 Oct, 2005.), p. 11).

"The whole idea is to come up with better approaches to give signals, to verify those signals [and] pursue them much earlier in the process," Corr stated.

"What we're not doing is [involving] industry," he noted. "The fact is, we ought to fit into the equation."

Corr criticized FDA for looking at one database, extracting a piece of information, and then applying that information to the whole pool, whether or not it is applicable. "What might be a signal for one database, may not invalidate an observation from another database," he noted.

To efficiently use the various databases, Corr suggested that "standards needed to be codified," terminology defined and "validated tools" developed to coordinate examination of data.

It is also essential for the agency to incorporate benefit information into its communication of risks, Corr suggested. "Safety is not defined by risk alone, but by the balance of risks and benefits....That's one of the major issues with Drug Watch: you see the risks, but it's not put in the context with the value and benefit."

Drug Watch "At Odds" With Function of FDA

"The biggest problem is that Drug Watch is entirely at odds with the entire function and purpose of FDA, which is to speak authoritatively," former FDA Chief Counsel Dan Troy (Sidley Austin Brown & Wood) said at the Windhover meeting.

People often argue that FDA should not be paternalistic, Troy said, but "it is a paternalistic agency. It decides whether or not a product can be put out, it decides what can be said about it."

"FDA had traditionally spoken authoritatively - it's the gold standard, once they say it, it's pretty well scientifically substantiated."

With Drug Watch, the agency wants to have it both ways: to provide transparency and speak authoritatively, Troy said.

Over time, putting out unsubstantiated information will lead to confusion and "dilute FDA's reputation and ability to speak authoritatively. It is completely at tension as a legal matter, and as a policy matter, with FDA's function."

Another problem with Drug Watch is that FDA refuses to work with sponsors, Troy said. With the existing proposal, the agency was planning to put information out there without advance notice to the sponsor, and was saying, "we will not work with sponsors."

The comments FDA has received on Drug Watch did not just "tilt" toward the negative, but were "overwhelmingly negative," Troy maintained. "I was very happy to hear from Steve Galson that they were going back to the drawing board on Drug Watch."

Crisis Of Communication, Or Enforcement?

"FDA really seems to have lost its confidence in its statutory risk management tools and information venues," Troy continued, suggesting that the agency has resorted to "extralegal" approaches.

FDA does not have the authority for a lot of the information it requests that it feels is necessary to the risk management policy, Troy stated. Examples include premarket comparative efficacy and safety studies, comparative safety studies, and safety studies for an off-label use which the company never intends to promote, Troy said.

"It is not illegal for you to agree to do something that FDA does not have the authority to require you to do, but it's extralegal in the sense that FDA cannot take action against you to force these risk management plans."

FDA cannot prohibit companies from direct-to-consumer advertising, require physician education programs, or restrict initial detailing to a target population or limit the number of sales representatives, Troy asserted.

Troy, however, noted that although he is "not a fan of risk management plans...I recognize the reality that you all need to consider them and in some cases they can be good business."